Phase II Study of DCA (Dichloroacetate) in Combination With Cisplatin and Definitive Radiation in Stage III-IV Squamous Cell Carcinoma of the Head and Neck

Trial Information

Phase II Study of DCA (Dichloroacetate) in Combination With Cisplatin and Definitive Radiation in Stage III-IV Squamous Cell Carcinoma of the Head and Neck

Doses for Cisplatin will be based on actual body weight taken on each day of Cisplatin
therapy. DCA doses will be calculated at baseline according to actual body weight and will
not change during the 8 weeks of therapy.

A careful description of the extent of the primary lesion and nodal spread will be recorded.

Dental Evaluation: Prior to treatment, patients will be evaluated by the dental service and
a prophylactic cleaning/fluoride regimen instituted. A delay of at least 14 days from major
surgery, including dental extractions, will be required prior to Day 1 treatment.

Airway Patency: Significant laryngeal edema has been described after the use of cisplatin
containing regimens. Patients with laryngeal tumors should be considered for a prophylactic
tracheostomy prior to the initiation of chemotherapy, if any possibility of airway
compromise exists. Patients with laryngeal tumors experiencing respiratory stridor or
compromise shortly after chemotherapy/radiotherapy administration should be rapidly
evaluated for tracheostomy.

Alimentation: Significant stomatitis, mucositis and dysphagia are expected with these
treatment regimens. Hospitalization may be required for symptomatic management. Pronounced
weight loss is common, and adequate alimentation needs to be maintained. Early, if not
pre-emptive, enteral tube feedings should be considered if difficulty is anticipated.

Compliance: The complexity of these treatment regimes and their attendant toxicity are such
that compliance is of major concern. Patients expected to pose compliance problems should
not be entered on this study. Patients will need to be seen at least weekly during therapy
so that the toxicities can be monitored and treated.

Inclusion Criteria:

- Patients must have histologically, cytologically confirmed and previously untreated
stage 3 or 4 HNSC that recommended treatment would be concurrent cisplatin and
radiation.

- Age ≥ 18 years

- ECOG performance status ≤ 2 or Karnofsky ≥70%

- Life expectancy of greater than 12 weeks.

- Patients must have normal organ and marrow function as defined below:

- The effects of DCA on the developing human fetus are unknown. For this reason and
because DCA can be teratogenic, women of child-bearing potential and men must agree
to use adequate contraception (e.g.: hormonal or barrier method of birth control,
abstinence)prior to study entry and for the duration of study participation. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.

- Ability to understand the purpose of the study and the willingness to sign a written
informed consent document.

- Repeat biopsy is not mandatory, but is strongly suggested. Should be performed
between Day 8 and Day 15 treatments.

Exclusion Criteria:

- Patients may not be receiving any other investigational agents, chemotherapy,
immunotherapy, radiotherapy, or molecular targeted agents.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that could confound the evaluation of neurologic and other adverse
events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to DCA.(Cetuximab)

- Due to the possibility of peripheral sensorimotor neuropathy from DCA, the presence
of grade 2 or higher peripheral neuropathy due to a prior medical condition (such as
multiple sclerosis), medications, or other etiologies.

- Any psychological, familial, sociological, or geographical conditions that do not
permit medical follow-up and compliance with the study protocol.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, diabetes mellitus, or psychiatric illness/social situations that would
limit compliance with study requirements. Specifically, for patients who are taking
either or both oral hypoglycemics and insulin for diabetes mellitus will not be
eligible as DCA in combination with these agents may increase the risk of clinically
significant hypoglycemia, compromising patient safety.

- Pregnant or breast-feeding women are excluded from this study because DCA is an agent
with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with DCA, breastfeeding should be discontinued if the mother
is treated with DCA.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with DCA. In addition, these patients
are at increased risk of lethal infections when treated with marrow-suppressive
therapy.

- Five years must have elapsed since the initial curative procedure for other
malignancies, except for in situ cervical cancer, basal cell carcinoma of the skin,
and localized prostate cancer after curative therapy such as surgery, or radiation.

- History of malabsorption syndrome or substantial amount of small bowels or stomach
removed that may impair absorption of DCA.

Study Design:

Outcome Measure:

To evaluate the safety of delivering DCA during primary chemo-radiation.

Outcome Description:

The safety objectives that will be monitored will include but are not limited to mucositis, leucopenia, neuropathy, and treatment breaks. This will be done according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

Outcome Time Frame:

A safety evaluation will be conducted after the first six patients are enrolled into the safety cohort, at approximately 7 months from study opening.

Safety Issue:

Yes

Principal Investigator

John H Lee, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sanford Health

Authority:

United States: Food and Drug Administration

Study ID:

DCA 2010

NCT ID:

NCT01386632

Start Date:

May 2011

Completion Date:

February 2013

Related Keywords:

Squamous Cell Carcinoma of the Head and Neck

Stage III-IV Squamous Cell Carcinoma

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Name

Location

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